Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chlorideinduced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/b-catenin signaling.

Xanthomonas oryzae pv. oryzicola, the causal agent of bacterial leaf streak, is one of the most important bacterial pathogens in rice. However, little is known about the functions of individual type III effectors in virulence and pathogenicity of X. oryzae pv. oryzicola. Here, we examined the effect of the mutations of 23 putative nontranscription activator-like effector genes on X. oryzae pv. oryzicola virulence. The avrBs2 knock-out mutant was significantly attenuated in virulence to rice. In contrast, the xopAA deletion caused enhanced virulence to a certain rice cultivar. It was also demonstrated that six putative effectors, including XopN, XopX, XopA, XopY, XopF1, and AvrBs2, caused the hypersensitive response on nonhost Nicotiana benthamiana leaves. Virulence function of AvrBs2 was further confirmed by transgenic technology. Pathogen-associated molecular pattern-triggered immune responses including the generation of reactive oxygen species and expression of pathogenesis-related genes were strongly suppressed in the AvrBs2-expressing transgenic rice lines. Although not inhibiting flg22-induced activation of mitogen-activated protein kinases, heterologous expression of AvrBs2 greatly promotes disease progression in rice caused by two important bacterial pathogens X. oryzae pvs. oryzae and oryzicola. Collectively, these results indicate that AvrBs2 is an essential virulence factor that contributes to X. oryzae pv. oryzicola virulence through inhibiting defense responses and promoting bacterial multiplication in monocot rice.

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